Optical coherence angiography for pre-treatment assessment and treatment monitoring following photodynamic therapy: a basal cell carcinoma patient study

Abstract

Microvascular networks of human basal cell carcinomas (Bcc) and surrounding skin were assessed with optical coherence angiography (ocA) in conjunction with photodynamic therapy (pDt). ocA images were collected and analyzed in 31 lesions pre-treatment, and immediately/24 hours/3-12 months posttreatment. Pre-treatment OCA enabled differentiation between prevalent subtypes of BCC (nodular and superficial) and nodular-with-necrotic-core BCC subtypes with a diagnostic accuracy of 78%; this can facilitate more accurate biopsy reducing sampling error and better therapy regimen selection. Post-treatment OCA images at 24 hours were 98% predictive of eventual outcome. Additional findings highlight the importance of pre-treatment necrotic core, vascular metrics associated with hypertrophic scar formation, and early microvascular changes necessary in both tumorous and peri-tumorous regions to ensure treatment success. Basal cell carcinoma (BCC) is the most common slow-growing locally invasive malignant epidermal skin tumor, with majority of the lesions localized on the head and neck 1. There are many different classification schemes for the BCC types and subtypes including nodular, superficial, infundibulocystic, fibroepithelial and the aggressive growth variants such as infiltrative, micronodular and morpheaform (sclerosing) plus some combinations 2,3. BCC treatment management starts with accurate diagnosis, including histopathology 4,5 and the development of reliable and non-invasive techniques for its diagnosis is crucial. Currently such non-invasive technologies have limited reliability and more development and validation work is needed 6. Dermatoscopy is a useful tool in the preoperative prediction of the BCC subtype 7. However, the evidence of its clinical diagnostic efficacy is somewhat limited and in ambiguous lesions, the BCC subtype has to be assessed histopathologically 8. Modern optical imaging modalities such as wide-field fluorescence imaging 9 , confocal microscopy 10 , optical coherence tomography (OCT) 11-13 , polarization-sensitive OCT 14,15 , OCT-based angiography (OCA) 16,17 and photoacoustic imaging 18 and their combinations 19,20 offer new possibilities for detection and visualization of human skin tumor structure and microvascular network in real time. OCT is particularly promising as it offers non-invasive structural and functional 3D imaging of biological tissues with high spatial resolution 11 , in particular for BCC 9,13,21. For the first time in this study, we used spectral domain OCT/OCA system to assess the after-treatment effects following photodynamic therapy (PDT) in patients with different BCC subtypes. PDT involves administration of photosensitizes which preferentially accumulate in malignant tissues, followed by local light activation at appropriate wavelength, producing oxygen free radicals and singlet oxygen 22. The generation of these reactive oxygen species subsequently causes tumor cell death by apoptosis, necrosis

In vivo assessment of functional and morphological alterations in tumors under treatment using OCT-angiography combined with OCT-elastography

“…For the first time we applied in combination OCA and OCE to test the ability these optical methods to in vivo predict tumor response. Another goal of the study was to estimate the universality of these approaches by applying each of these methods to another type of tumor and another type of therapy in comparison with previous, partially similar, applications of OCA and OCE [5,6,19,26,27].…”

“…Among the methods of detection, visualization and quantitative assessment/monitoring of tumor microcirculation (perfusion) OCT-based angiography (OCA) has demonstrated high potential [5,6,[14][15][16][17][18]. Recently, observation of blood-circulation blockages in tumors and in peri-tumorous regions based on OCA has proven to be very useful for accurate prediction of the outcome of vasculature-targeted PDT during the first 24 hours post-PDT on experimental animals [5,6] and patients [19], as well as for detection of side effects of radio-therapy manifested via microvasculature alterations in the oral cavity [16]. However, unlike the fairly easily observed perturbation in the microcirculation of blood, the assessment of the histological structure of tissues lacks precise, non-invasive methods.…”

“…It was treated by two different vasculature-targeted therapies -bevacizumabbased ChT and PDT, the results of the latter being assessed by OCE for the first time. In parallel, to verify universality of OCA that previously proved to be very efficient for early assessment of PDT [6,19] and radiation therapy [16], for the first time OCA was applied to assess anti-angiogenic chemotherapy. Therefore, to enable complex evaluation of tumor reaction to therapies, in this study we combined for the first time in vivo functional characterization (by observing blood flow alterations using OCA) with in vivo assessment of microstructural/morphological alterations (using OCE-segmentation) as described in the following sections.…”

Histological validation of in vivo assessment of cancer tissue inhomogeneity and automated morphological segmentation enabled by Optical Coherence Elastography

“…Certainly, the OCE method may be also useful in combination with subsequent conventional histology to facilitate the recognition of areas in the tissue with changes that may be missed during routine microscopic examination. A more complete assessment of the tumor response and thereby the effectiveness of treatment can be achieved by combining OCE with other modalities based on the same OCT setup (angiography 67,68 , polarization-sensitive OCT 5 , estimation of the optical-signal decay 69 , etc.). www.nature.com/scientificreports/ Knowing both the advantages and the limitations of the OCE method (first of all, limited depth of scanning typical of OCT), it can be concluded that the method can be valuable in the study of surface structures (skin and mucous, where a biopsy is limited or not advisable) and the effects of various destructive or therapeutic/cosmetic agents on them.…”

“…Certainly, the OCE method may be also useful in combination with subsequent conventional histology to facilitate the recognition of areas in the tissue with changes that may be missed during routine microscopic examination. A more complete assessment of the tumor response and thereby the effectiveness of treatment can be achieved by combining OCE with other modalities based on the same OCT setup (angiography 67 , 68 , polarization-sensitive OCT 5 , estimation of the optical-signal decay 69 , etc.).…”